NM_015147.3:c.1884+638C>T

Variant names:

• chr2-65073618-C-T
• rs12621608
• NM_015147.3:c.1884+638C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015147.3(CEP68):​c.1884+638C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 161,052 control chromosomes in the GnomAD database, including 2,767 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2612 hom., cov: 32)
  • Exomes 𝑓: 0.18 (155 hom.)
• Consequence: CEP68 NM_015147.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 4 publications found

Genes affected

CEP68 (HGNC:29076): (centrosomal protein 68) Enables protein domain specific binding activity and protein kinase binding activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RAB1A (HGNC:9758): (RAB1A, member RAS oncogene family) This gene encodes a member of the Ras superfamily of GTPases. Members of the gene family cycle between inactive GDP-bound and active GTP-bound forms. This small GTPase controls vesicle traffic from the endoplasmic reticulum to the Golgi apparatus. Multiple alternatively spliced transcript variants have been identified for this gene which encode different protein isoforms. [provided by RefSeq, Oct 2008]

RAB1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015147.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	NM_015147.3	MANE Select	c.1884+638C>T		intron	N/A	NP_055962.2	Q76N32-1
	CEP68	NM_001319100.2		c.1884+638C>T		intron	N/A	NP_001306029.1	Q76N32-1
	CEP68	NM_001410838.1		c.1884+638C>T		intron	N/A	NP_001397767.1	A0A994J4E5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP68	ENST00000377990.7	TSL:1 MANE Select	c.1884+638C>T		intron	N/A	ENSP00000367229.2	Q76N32-1
	CEP68	ENST00000260569.4	TSL:1	c.1474-664C>T		intron	N/A	ENSP00000260569.4	Q76N32-2
	CEP68	ENST00000537589.1	TSL:1	n.2238C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25473 AN: 152136 Hom.: 2602 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.175 AC: 1541 AN: 8798 Hom.: 155 Cov.: 0 AF XY: 0.170 AC XY: 767 AN XY: 4512

African (AFR) AF: 0.00 AC: 0 AN: 34

American (AMR) AF: 0.191 AC: 335 AN: 1752

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 13 AN: 46

East Asian (EAS) AF: 0.274 AC: 63 AN: 230

South Asian (SAS) AF: 0.226 AC: 202 AN: 894

European-Finnish (FIN) AF: 0.0923 AC: 12 AN: 130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.161 AC: 861 AN: 5332

Other (OTH) AF: 0.150 AC: 55 AN: 366

GnomAD4 genome AF: 0.167 AC: 25499 AN: 152254 Hom.: 2612 Cov.: 32 AF XY: 0.170 AC XY: 12672 AN XY: 74408

African (AFR) AF: 0.0699 AC: 2905 AN: 41572

American (AMR) AF: 0.210 AC: 3218 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1055 AN: 3472

East Asian (EAS) AF: 0.334 AC: 1730 AN: 5178

South Asian (SAS) AF: 0.288 AC: 1392 AN: 4826

European-Finnish (FIN) AF: 0.178 AC: 1887 AN: 10600

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12617 AN: 67996

Other (OTH) AF: 0.211 AC: 446 AN: 2116

Alfa AF: 0.178 Hom.: 440

Bravo AF: 0.166

Asia WGS AF: 0.366 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.79
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12621608; hg19: chr2-65300752;